Acute myocardial infarction (AMI) accounts for the majority of morbidity and mortality in industrialized countries. Autopsy studies have demonstrated that certain atherosclerotic plaque types, termed "vulnerable plaques," are more commonly identified in post-MI patients. These plaques are not angiographically stenotic and consist of a macrophage-laden thin fibrous cap overlying a large lipid rich core. While it is currently thought that patients with vulnerable plaques are at a higher risk for plaque rupture and acute coronary thrombosis, this hypothesis has not been prospectively tested, and the clinical significance of a vulnerable plaque is currently unknown. Clinical studies to determine the prevalence, incidence, and natural history of these lesions have not been conducted due to the lack of a method for identifying vulnerable plaques in living human patients, Furthermore, since these plaques have only been studied postmortem, little is known about the morphology of plaques prior to rupture. We have previously demonstrated that intracoronary optical coherence tomography (OCT) is capable of accurately identifying all of the microscopic features of vulnerable plaques. Due to the slow image acquisition rate of existing imaging technology, however, current studies have been limited exclusively to imaging discrete coronary locations in patients. We present preliminary data demonstrating a new paradigm for OCT that enables continuous imaging of long coronary segments by vastly increasing imaging speed. The goal of the proposed work is to apply this new technology in a multiple time point clinical study to investigate the incidence, prevalence, and natural history of vulnerable plaques and determine the morphologic predictors of AMI. The impact of this program will be high, as it will provide 1) a diagnostic tool that is capable of identifying high-risk plaques prior to the occurrence of an acute coronary event, and 2) the knowledge required to determine the optimal therapeutic strategy for these lesions.